Randomized Trial of Focused Ultrasound Subthalamotomy for Parkinson's Disease.

BACKGROUND: The subthalamic nucleus is the preferred neurosurgical target for deep-brain stimulation to treat cardinal motor features of Parkinson's disease. Focused ultrasound is an imaging-guided method for creating therapeutic lesions in deep-brain structures, including the subthalamic nucleus. METHODS: We randomly assigned, in a 2:1 ratio, patients with markedly asymmetric Parkinson's disease who had motor signs not fully controlled by medication or who were ineligible for deep-brain stimulation surgery to undergo focused ultrasound subthalamotomy on the side opposite their main motor signs or a sham procedure. The primary efficacy outcome was the between-group difference in the change from baseline to 4 months in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor score (i.e., part III) for the more affected body side (range, 0 to 44, with higher scores indicating worse parkinsonism) in the off-medication state. The primary safety outcome (procedure-related complications) was assessed at 4 months. RESULTS: Among 40 enrolled patients, 27 were assigned to focused ultrasound subthalamotomy (active treatment) and 13 to the sham procedure (control). The mean MDS-UPDRS III score for the more affected side decreased from 19.9 at baseline to 9.9 at 4 months in the active-treatment group (least-squares mean difference, 9.8 points; 95% confidence interval [CI], 8.6 to 11.1) and from 18.7 to 17.1 in the control group (least-squares mean difference, 1.7 points; 95% CI, 0.0 to 3.5); the between-group difference was 8.1 points (95% CI, 6.0 to 10.3; P<0.001). Adverse events in the active-treatment group were dyskinesia in the off-medication state in 6 patients and in the on-medication state in 6, which persisted in 3 and 1, respectively, at 4 months; weakness on the treated side in 5 patients, which persisted in 2 at 4 months; speech disturbance in 15 patients, which persisted in 3 at 4 months; facial weakness in 3 patients, which persisted in 1 at 4 months; and gait disturbance in 13 patients, which persisted in 2 at 4 months. In 6 patients in the active-treatment group, some of these deficits were present at 12 months. CONCLUSIONS: Focused ultrasound subthalamotomy in one hemisphere improved motor features of Parkinson's disease in selected patients with asymmetric signs. Adverse events included speech and gait disturbances, weakness on the treated side, and dyskinesia. (Funded by Insightec and others; ClinicalTrials.gov number, NCT03454425.).

Stereotactic and Functional Neurosurgery Convection-Enhanced Delivery of Autologous Cerebrospinal Fluid Enhances Basal Ganglia Visualization during MRI-Guided Deep Brain Stimulation Surgery.

INTRODUCTION: The aim of this study was to determine the safety and feasibility of convection-enhanced delivery of autologous cerebrospinal fluid (CSF) for enhancing intraoperative magnetic resonance imaging (MRI) of the basal ganglia during stereotactic neurosurgery. METHODS: This pilot study was conducted in 4 patients with Parkinson's disease (PD) who underwent MRI-guided deep brain stimulation of the globus pallidus internus (GPi). CSF was obtained via lumbar puncture after general anesthesia and prior to incision. A frameless stereotaxy system was installed, and an infusion catheter was inserted to the GPi using intraoperative MRI. Infusion of autologous CSF was performed at a convective rate of 5 µL/min with a maximum volume of infusion (Vi) of 500 mL. T2-weighted MRI scans were obtained every 15 min up to a maximum of 105 min in order to calculate the volume of distribution (Vd). Safety was assessed with adverse event monitoring, and clinical outcomes were measured with changes in unmedicated UPDRS part III and PDQ-39 scores from baseline to 6 months postoperatively. RESULTS: All four infusions were safe and without adverse events. The mean unmedicated UPDRS part III and PDQ-39 scores improved by 24% and 26%, respectively. The Vd:Vi ratio ranged from 2.2 to 2.8 and peaked 45 min from the onset of infusion, which is when the borders of the GPi could generally be visualized based on T2-weighted MRI. Two patients underwent refinement of the stereotactic targeting based on infusion-enhanced images. CONCLUSIONS: The convective administration of autologous CSF to deep brain structures appears safe and feasible for enhancing intraoperative MRI during stereotactic procedures. Infusion-enhanced imaging with target-specific infusates could be developed to visualize neurochemical circuits or cellular regions that currently are not seen with anatomic/structural MRI.

A Randomized Trial of Focused Ultrasound Thalamotomy for Essential Tremor.

BACKGROUND: Uncontrolled pilot studies have suggested the efficacy of focused ultrasound thalamotomy with magnetic resonance imaging (MRI) guidance for the treatment of essential tremor. METHODS: We enrolled patients with moderate-to-severe essential tremor that had not responded to at least two trials of medical therapy and randomly assigned them in a 3:1 ratio to undergo unilateral focused ultrasound thalamotomy or a sham procedure. The Clinical Rating Scale for Tremor and the Quality of Life in Essential Tremor Questionnaire were administered at baseline and at 1, 3, 6, and 12 months. Tremor assessments were videotaped and rated by an independent group of neurologists who were unaware of the treatment assignments. The primary outcome was the between-group difference in the change from baseline to 3 months in hand tremor, rated on a 32-point scale (with higher scores indicating more severe tremor). After 3 months, patients in the sham-procedure group could cross over to active treatment (the open-label extension cohort). RESULTS: Seventy-six patients were included in the analysis. Hand-tremor scores improved more after focused ultrasound thalamotomy (from 18.1 points at baseline to 9.6 at 3 months) than after the sham procedure (from 16.0 to 15.8 points); the between-group difference in the mean change was 8.3 points (95% confidence interval [CI], 5.9 to 10.7; P<0.001). The improvement in the thalamotomy group was maintained at 12 months (change from baseline, 7.2 points; 95% CI, 6.1 to 8.3). Secondary outcome measures assessing disability and quality of life also improved with active treatment (the blinded thalamotomy cohort)as compared with the sham procedure (P<0.001 for both comparisons). Adverse events in the thalamotomy group included gait disturbance in 36% of patients and paresthesias or numbness in 38%; these adverse events persisted at 12 months in 9% and 14% of patients, respectively. CONCLUSIONS: MRI-guided focused ultrasound thalamotomy reduced hand tremor in patients with essential tremor. Side effects included sensory and gait disturbances. (Funded by InSightec and others; ClinicalTrials.gov number, NCT01827904.).

A prospective trial of magnetic resonance-guided focused ultrasound thalamotomy for essential tremor: Results at the 2-year follow-up.

OBJECTIVE: Magnetic resonance guided focused ultrasound (MRgFUS) has recently been investigated as a new treatment modality for essential tremor (ET), but the durability of the procedure has not yet been evaluated. This study reports results at a 2- year follow-up after MRgFUS thalamotomy for ET. METHODS: A total of 76 patients with moderate-to-severe ET, who had not responded to at least two trials of medical therapy, were enrolled in the original randomized study of unilateral thalamotomy and evaluated using the clinical rating scale for tremor. Sixty-seven of the patients continued in the open-label extension phase of the study with monitoring for 2 years. Nine patients were excluded by 2 years, for example, because of alternative therapy such as deep brain stimulation (n = 3) or inadequate thermal lesioning (n = 1). However, all patients in each follow-up period were analyzed. RESULTS: Mean hand tremor score at baseline (19.8 ± 4.9; 76 patients) improved by 55% at 6 months (8.6 ± 4.5; 75 patients). The improvement in tremor score from baseline was durable at 1 year (53%; 8.9 ± 4.8; 70 patients) and at 2 years (56%; 8.8 ± 5.0; 67 patients). Similarly, the disability score at baseline (16.4 ± 4.5; 76 patients) improved by 64% at 6 months (5.4 ± 4.7; 75 patients). This improvement was also sustained at 1 year (5.4 ± 5.3; 70 patients) and at 2 years (6.5 ± 5.0; 67 patients). Paresthesias and gait disturbances were the most common adverse effects at 1 year-each observed in 10 patients with an additional 5 patients experiencing neurological adverse effects. None of the adverse events worsened over the period of follow-up, and 2 of these resolved. There were no new delayed complications at 2 years. INTERPRETATION: Tremor suppression after MRgFUS thalamotomy for ET is stably maintained at 2 years. Latent or delayed complications do not develop after treatment. Ann Neurol 2018;83:107-114.

The role of high-intensity focused ultrasound as a symptomatic treatment for Parkinson's disease.

MR-guided focused ultrasound is a novel, minimally invasive surgical procedure for symptomatic treatment of PD. With this technology, the ventral intermediate nucleus, STN, and internal globus pallidus have been targeted for therapeutic cerebral ablation, while also minimizing the risk of hemorrhage and infection from more invasive neurosurgical procedures. In a double-blinded, prospective, sham-controlled randomized controlled trial of MR-guided focused ultrasound thalamotomy for treatment of tremor-dominant PD, 62% of treated patients demonstrated improvement in tremor scores from baseline to 3 months postoperatively, as compared to 22% in the sham group. There has been only one open-label trial of MR-guided focused ultrasound subthalamotomy for patients with PD, demonstrating improvements of 71% for rigidity, 36% for akinesia, and 77% for tremor 6 months after treatment. Among the two open-label trials of MR-guided focused ultrasound pallidotomy for patients with PD, dyskinesia and overall motor scores improved up to 52% and 45% at 6 months postoperatively. Although MR-guided focused ultrasound thalamotomy is now approved by the U.S. Food and Drug Administration for treatment of parkinsonian tremor, additional high-quality randomized controlled trials are warranted and are underway to determine the safety and efficacy of MR-guided focused ultrasound subthalamotomy and pallidotomy for treatment of the cardinal features of PD. These studies will be paramount to aid clinicians to determine the ideal ablative target for individual patients. Additional work will be required to assess the durability of MR-guided focused ultrasound lesions, ideal timing of MR-guided focused ultrasound ablation in the course of PD, and the safety of performing bilateral lesions. © 2019 International Parkinson and Movement Disorder Society.

Gamma Knife Radiosurgery for Trigeminal Neuralgia Reduces Neurovascular Compression: A Case Report after 11 Years.

BACKGROUND: Trigeminal neuralgia (TN) is a rare and debilitating craniofacial pain syndrome often caused by vascular compression of the trigeminal nerve. Gamma Knife radiosurgery (GKRS) has been shown to offer a less invasive yet effective treatment method for pain reduction in TN. In this case report, we observed radiological evidence of resolved neurovascular compression after 11 years for a patient with recur-rent TN and prior GKRS. CASE REPORT: A 72-year-old -female presented with TN and radiological evidence of neurovas-cular compression on the affected side. She had complete resolution of her pain for 7 years after treatment with GKRS. The patient experienced recurrence and underwent repeat GKRS, this time resulting in another 3 years of pain relief. After the second recurrence, repeat intracranial imaging demonstrated resolution of neurovascular compression. DISCUSSION: GKRS is an important treatment option for TN, although the mechanisms behind pain relief from this procedure still remain unclear. While prior histological and radiological studies point to ablative mechanisms for pain relief, this case report suggests that GKRS may result in a decompressive effect in TN due to changes in neurovascular architecture. Despite this finding, TN is known to occur and recur in the absence of neurovascular compression; thus, further work is necessary to understand the etiology of TN and its treatments. CONCLUSION: In this case, we demonstrate that vessel-nerve relationships may change over time in TN patients treated with GKRS, which raises the possibility that GKRS could ease a neurovascular compression.

Essential Tremor.

This JAMA Insights discusses the diagnostic evaluation and treatment, including pharmacological, nonpharmacological, and surgical options, of essential tremor.

A spiral-based volumetric acquisition for MR temperature imaging.

PURPOSE: To develop a rapid pulse sequence for volumetric MR thermometry. METHODS: Simulations were carried out to assess temperature deviation, focal spot distortion/blurring, and focal spot shift across a range of readout durations and maximum temperatures for Cartesian, spiral-out, and retraced spiral-in/out (RIO) trajectories. The RIO trajectory was applied for stack-of-spirals 3D imaging on a real-time imaging platform and preliminary evaluation was carried out compared to a standard 2D sequence in vivo using a swine brain model, comparing maximum and mean temperatures measured between the two methods, as well as the temporal standard deviation measured by the two methods. RESULTS: In simulations, low-bandwidth Cartesian trajectories showed substantial shift of the focal spot, whereas both spiral trajectories showed no shift while maintaining focal spot geometry. In vivo, the 3D sequence achieved real-time 4D monitoring of thermometry, with an update time of 2.9-3.3 s. CONCLUSION: Spiral imaging, and RIO imaging in particular, is an effective way to speed up volumetric MR thermometry. Magn Reson Med 79:3122-3127, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Neurological adverse event profile of magnetic resonance imaging-guided focused ultrasound thalamotomy for essential tremor.

BACKGROUND: Magnetic resonance imaging-guided focused ultrasound thalamotomy is approved by the U.S. Food and Drug Administration for treatment of essential tremor. Although this incisionless technology creates an ablative lesion, it potentially avoids serious complications of open stereotactic surgery. OBJECTIVE: To determine the safety profile of magnetic resonance imaging-guided focused ultrasound unilateral thalamotomy for essential tremor, including frequency, and severity of adverse events, including serious adverse events. METHODS: Analysis of safety data for magnetic resonance imaging-guided focused ultrasound thalamotomy (186 patients, five studies). RESULTS: Procedure-related serious adverse events were very infrequent (1.6%), without intracerebral hemorrhages or infections. Adverse events were usually transient and were commonly rated as mild (79%) and rarely severe (1%). As previously reported, abnormalities in sensation and balance were the commonest thalamotomy-related adverse events. CONCLUSION: The overall safety profile of magnetic resonance imaging-guided focused ultrasound thalamotomy supports its role as a new option for patients with medically refractory essential tremor. © 2018 International Parkinson and Movement Disorder Society.

Capgras Syndrome in Advanced Parkinson's Disease.

Psychosis is common in Parkinson's disease (PD), especially in advanced disease, and can lead to a number of psychotic symptoms, including delusions. One uncommon delusion is Capgras syndrome (CS). The authors report on three PD patients with a history of deep brain stimulation (DBS) who developed this delusion. The anatomic targets in these three patients were the subthalamic nuclei in two patients and the globus pallidus interna in one patient. The length of time between surgery and development of CS varied but was greater than 6 months. Additionally, all three patients showed evidence of impaired cognition prior to development of CS. Therefore, due to the length of time between DBS and CS in all three cases and the fact that one patient developed CS months after DBS explanation, DBS does not appear to be associated with CS. Given the distressing nature of this condition, patients with advanced PD who undergo DBS should be regularly screened for symptoms of psychosis with awareness of CS as a potential form.

Thalamic Deep Brain Stimulation Salvages Failed Focused Ultrasound Thalamotomy for Essential Tremor: A Case Report.

BACKGROUND: A recent randomized controlled trial investigating unilateral MRI-guided focused ultrasound (FUS) for essential tremor demonstrated efficacy. The long-term durability of this thalamotomy, however, is unknown. Furthermore, the feasibility of stimulating a previously lesioned target such as the thalamic nucleus ventralis intermedius (Vim) is poorly understood. We report a case of tremor recurrence, following an initially successful FUS thalamotomy, in which Vim-DBS was subsequently utilized to regain tremor control. METHODS: An 81-year-old right-handed female with medically refractory essential tremor (a Clinical Rating Scale for Tremor [CRST] value of 73) underwent left-sided FUS thalamotomy with initial abolition of right-upper extremity tremor. By the 6-month follow-up, there was complete recurrence of tremor (a CRST value of 76). The patient subsequently underwent left-sided Vim-DBS. RESULTS: Vim-DBS provided clinical improvement with a CRST value of 42 at the 3-month follow-up; the patient continues to do clinically well at the 6-month follow-up. This result mirrors previous reported cases of stimulation following radiofrequency and gamma-knife lesioning. Our literature review highlights several reasons for the waning of clinical benefit seen with lesional procedures. CONCLUSION: This case demonstrates that thalamic DBS can salvage a failed FUS thalamotomy and also the feasibility of stimulating a previously lesioned target.

Predicting lesion size during focused ultrasound thalamotomy: a review of 63 lesions over 3 clinical trials.

OBJECTIVE The goal of this study was to improve the predictability of lesion size during focused ultrasound (FUS) thalamotomy procedures. METHODS Treatment profiles and T2-weighted MRI (T2 MRI) studies obtained in 63 patients who participated in 3 clinical trials of FUS thalamotomy from February 2011 to March 2015 were reviewed retrospectively. Four damage estimate models were compared with lesion sizes measured on postprocedural T2 MRI. Models were based on 54°C × 3 seconds, 240 cumulative equivalent minutes at 43°C, and simple thermal threshold analysis, which recorded the maximum diameter that reached a temperature of at least 51°C and 54°C. Energy requirements per °C thermal rise above 37°C were also recorded. RESULTS Lesion diameters from T2 MRI correlated poorly from the day of the procedure to day 1 postprocedure (mean increase 78% [SD 79%]). There was more predictability of lesion size from day 1 to day 30, with a mean reduction in lesion diameter of 11% (SD 24%). Of the 4 models tested, the most correlative model to day 1 findings on T2 MRI was a 51°C threshold. The authors observed an increase in the energy requirement for each subsequent treatment sonication, with the largest percentage increase from treatment sonication 1 to treatment sonication 2 (mean increase 20% in energy required per °C increase in temperature above 37°C). CONCLUSIONS At the margins, 51°C temperature threshold diameters correlated best to lesion diameters measured at day 1 with T2 MRI. The lesion size from T2 MRI decreases from day 1 to day 30 in a predictable manner, much more so than from the day of the procedure to day 1 postprocedure. Energy requirements per °C rise above 37°C continuously increase with each successive sonication.

Deep brain stimulation for the treatment of drug addiction.

Drug addiction represents a significant public health concern that has high rates of relapse despite optimal medical therapy and rehabilitation support. New therapies are needed, and deep brain stimulation (DBS) may be an effective treatment. The past 15 years have seen numerous animal DBS studies for addiction to various drugs of abuse, with most reporting decreases in drug-seeking behavior with stimulation. The most common target for stimulation has been the nucleus accumbens, a key structure in the mesolimbic reward pathway. In addiction, the mesolimbic reward pathway undergoes a series of neuroplastic changes. Chief among them is a relative hypofunctioning of the prefrontal cortex, which is thought to lead to the diminished impulse control that is characteristic of drug addiction. The prefrontal cortex, as well as other targets involved in drug addiction such as the lateral habenula, hypothalamus, insula, and subthalamic nucleus have also been stimulated in animals, with encouraging results. Although animal studies have largely shown promising results, current DBS studies for drug addiction primarily use stimulation during active drug use. More data are needed on the effect of DBS during withdrawal in preventing future relapse. The published human experience for DBS for drug addiction is currently limited to several promising case series or case reports that are not controlled. Further animal and human work is needed to determine what role DBS can play in the treatment of drug addiction.

Transcranial magnetic resonance imaging-guided focused ultrasound thalamotomy for tremor: technical note.

Although the use of focused ultrasound (FUS) in neurosurgery dates to the 1950s, its clinical utility was limited by the need for a craniotomy to create an acoustic window. Recent technological advances have enabled efficient transcranial delivery of US. Moreover, US is now coupled with MRI to ensure precise energy delivery and monitoring. Thus, MRI-guided transcranial FUS lesioning is now being investigated for myriad neurological and psychiatric disorders. Among the first transcranial FUS treatments is thalamotomy for the treatment of various tremors. The authors provide a technical overview of FUS thalamotomy for tremor as well as important lessons learned during their experience with this emerging technology.

The emerging role of transcranial magnetic resonance imaging-guided focused ultrasound in functional neurosurgery.

To review the emerging role of transcranial MR-guided focused ultrasound as a treatment and research modality for functional neurological disorders, we summarize recent clinical and preclinical studies. Clinical trials have investigated the safety and efficacy of thermal lesions created by transcranial, high-intensity focused ultrasound. Preclinical work has additionally investigated the ability to disrupt the blood-brain barrier and to produce reversible neuromodulation with focused ultrasound utilizing lower intensities. We discuss ongoing trials and future avenues of investigation. © 2016 International Parkinson and Movement Disorder Society.

A pilot study of focused ultrasound thalamotomy for essential tremor.

BACKGROUND: Recent advances have enabled delivery of high-intensity focused ultrasound through the intact human cranium with magnetic resonance imaging (MRI) guidance. This preliminary study investigates the use of transcranial MRI-guided focused ultrasound thalamotomy for the treatment of essential tremor. METHODS: From February 2011 through December 2011, in an open-label, uncontrolled study, we used transcranial MRI-guided focused ultrasound to target the unilateral ventral intermediate nucleus of the thalamus in 15 patients with severe, medication-refractory essential tremor. We recorded all safety data and measured the effectiveness of tremor suppression using the Clinical Rating Scale for Tremor to calculate the total score (ranging from 0 to 160), hand subscore (primary outcome, ranging from 0 to 32), and disability subscore (ranging from 0 to 32), with higher scores indicating worse tremor. We assessed the patients' perceptions of treatment efficacy with the Quality of Life in Essential Tremor Questionnaire (ranging from 0 to 100%, with higher scores indicating greater perceived disability). RESULTS: Thermal ablation of the thalamic target occurred in all patients. Adverse effects of the procedure included transient sensory, cerebellar, motor, and speech abnormalities, with persistent paresthesias in four patients. Scores for hand tremor improved from 20.4 at baseline to 5.2 at 12 months (P=0.001). Total tremor scores improved from 54.9 to 24.3 (P=0.001). Disability scores improved from 18.2 to 2.8 (P=0.001). Quality-of-life scores improved from 37% to 11% (P=0.001). CONCLUSIONS: In this pilot study, essential tremor improved in 15 patients treated with MRI-guided focused ultrasound thalamotomy. Large, randomized, controlled trials will be required to assess the procedure's efficacy and safety. (Funded by the Focused Ultrasound Surgery Foundation; ClinicalTrials.gov number, NCT01304758.).

Deep Brain Stimulation in the Setting of Cochlear Implants: Case Report and Literature Review.

BACKGROUND/AIMS: As technology continues to advance for our aging population, an increasing number of deep brain stimulation (DBS) candidates will have preexisting implanted electrical devices. In this article, we discuss safe and successful DBS in a patient with Parkinson's disease (PD) and bilateral cochlear implants. METHODS: A 70-year-old male with PD and bilateral cochlear implants underwent successful microelectrode-guided DBS implantation into bilateral subthalamic nuclei (STN). The patient's cochlear implant magnets were removed and replaced in the outpatient clinic for preoperative MRI and stereotactic targeting. The cochlear implants were turned off intraoperatively for STN microelectrode recordings. RESULTS: Precise, MRI-guided stereotactic DBS implantation was possible. Intraoperative high-fidelity microelectrode recordings confirmed STN neurons with the cochlear implants turned off. These recordings were not possible with active cochlear implant devices. Our literature review describes the other approaches/techniques that have been used to manage DBS surgery in the setting of cochlear implants. CONCLUSIONS: Despite the risk of electrical interference between implanted medical devices, DBS and cochlear implants may be safe and compatible in the same patient if necessary precautions are taken.

Feasibility and Safety of MR-Guided Focused Ultrasound Lesioning in the Setting of Deep Brain Stimulation.

BACKGROUND: Patients treated with deep brain stimulation (DBS) often develop symptom progression. If safe, focused ultrasound (FUS) lesioning could be used for patients unable to undergo further DBS surgery. OBJECTIVE: To test the feasibility and safety of MR-guided FUS surgery in the setting of a previously implanted DBS system. METHODS: Three preclinical experiments were designed to test feasibility and safety. Hydrogels were implanted with an electrode, and FUS lesions were targeted adjacently. Cadavers were implanted with a thalamic electrode, and FUS lesions were targeted in the contralateral thalamus. Finally, DBS systems were implanted in swine, and FUS lesioning was targeted to the contralateral thalamus, MRI was used to assess the treatments, and histological analyses were performed at 2 days and at 1 month. RESULTS: In gel experiments and cadavers, FUS resulted in target heating to 29-32°C without any heating at the electrode. In animal experiments, there were no FUS-related MRI signal changes near the electrode. Histological analysis showed typical FUS lesions with no evidence of damage surrounding the electrode tracts. CONCLUSIONS: FUS is feasible in the setting of a preimplanted DBS device. There was minimal heating of the device during the procedure and no apparent FUS-related tissue injury. © 2015 S. Karger AG, Basel.

Tremor.

Tremor, defined as a rhythmic and involuntary movement of any body part, is the most prevalent movement disorder, affecting millions of people in the United States. All adults have varying degrees of physiological tremor so it is imperative to distinguish physiological tremor from pathological tremor types. Tremor is not inherently dangerous, but it can cause significant disability at home and in the workplace. Common tremors like essential tremor and Parkinson disease tremor can be recognized by most clinicians at the early stages for the initiation of disease-specific medical therapies. Less common tremors, such as those induced by drugs or brain lesions, are also important to recognize because they may be more refractory to medical therapies and may require earlier referral to a neurological specialist. In patients with the most progressive and severe tremors that are resistant to medical therapies, surgical interventions are available and typically target deep brain regions with stimulation or lesioning. This Grand Rounds review describes the evaluation and evidence-based management of the most common tremors, essential tremor and Parkinson disease tremor.